Biomarkers.

Background: Obstructive sleep apnea (OSA) is associated with hypoxia-induced neuronal impairment and dysfunction-key risk factors for the pathogeneses of age-related neurodegenerative diseases such as Alzheimer's disease (AD). This study examined longitudinal associations between OSA severity and CSF biomarkers associated with AD, synaptic dysfunction, and neuroinflammation in a sample of late-middle-aged adults with increased risk for AD.

Method: N=25 cognitively unimpaired adults (64% female, mean age 65.

Biomarkers.

Background: Alzheimer disease (AD) related cognitive decline occurs at relatively young ages in individuals with Down syndrome (DS, early-mid 50s) and in those with autosomal dominant mutations (ADAD, 40-50s). Both groups show similar patterns of amyloid accumulation. We examined if brain volumes are similarly affected by AD pathology in individuals with DS and ADAD.

Biomarkers.

Background: Increased stress, a proposed risk factor for Alzheimer's disease (AD), is associated with increased brain and cognitive vulnerabilities in older populations, which may be different in women and men.

Objective: To examine cross-sectional associations between circulating stress hormones (epinephrine, norepinephrine, cortisol, dehydroepiandrosterone sulfate (DHEAS), and DHEAS/cortisol ratio) and multimodal measures of brain health and cognition sensitive to AD.

Method: 132 cognitively unimpaired older participants without clinical depression (age = 74.

Biomarkers.

Background: To support diagnosis of Alzheimer's disease (AD), concentrations of Aβ, tTau and pTau(181) and the Aβ/Aβ ratio are determined in cerebrospinal fluid (CSF). To increase standardization and comparability between diagnostic laboratories, certified reference material (CRM) is used to evaluate the trueness of novel assays. Due to lack of CRMs for tTau, pTau(181), and Aβ, comparability may be assessed by comparing assays from different manufacturers.

Biomarkers.

Background: Amyloid PET imaging is an established diagnostic tool for Alzheimer's disease, but its successful integration into clinical practice requires a comprehensive understanding of its impact on patients and the healthcare system. In 2022, the coverage with evidence development (CED) ENABLE study has been approved by the German Federal Joint Committee (trial registration: DRKS00030839). The study is scheduled to start in early 2024.

Biomarkers.

Background: Co-pathology between Alzheimer's disease (AD), Parkinson's disease (PD), and dementia with Lewy bodies (DLB) remains poorly understood but is relevant for trial design. We aimed to compare CSF markers of amyloid, tau, and neurodegeneration (ATN) and α-synuclein between AD, PD, DLB and controls, and investigate the influence of demographical, genetic, and clinical factors on amyloid positivity.

Method: As part of the EPND study, we included 337 individuals with AD, PD, DLB and controls from 6 centers.

Biomarkers.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by cognitive decline, memory loss, and impaired daily functioning. As the global population ages, the prevalence of AD continues to rise, emphasising the urgent need for effective preventive and therapeutic strategies. Carotenoids, a group of naturally occurring pigments with antioxidant properties, have gained attention for their potential neuroprotective effects.

Fast response solid electrolyte oxygen sensors with porous thin film electrodes.

A novel solid electrolyte sensor with considerably improved response times is presented. The new so-called eFIPEX [etched flux (Φ) probe experiment] is based on the FIPEX [flux (Φ) probe experiment] sensor applied for the measurement of molecular and atomic oxygen concentrations. A main application is the measurement of atmospheric atomic oxygen aboard sounding rockets up to altitudes of 250 km.

Biomarkers.

Background: MRI offers potential noninvasive detection of Alzheimer's micropathology. The AD hippocampus exhibits microscopic pathological changes such as tau tangles, iron accumulation and late-stage amyloid. Validating these changes from ultra-high-resolution ex-vivo MRI through histology is challenging due to nonlinear 3D deformations between MRI and histological samples.

Biomarkers.

Background: Understanding modulators of Alzheimer's disease's (AD) progression is crucial for determining optimal treatment windows and targets. Apolipoprotein E ε4 (ApoE4), i.e.

Biomarkers.

Background: Widely used neuropsychological test instruments are notoriously biased across the demographics of age, sex/gender, education, language and culture. This includes verbal memory tests that elicit speech such as the paragraph recall or list-learning memory tests. Language tests are similarly biased, including the Boston Diagnostic Aphasia Examination Cookie Theft Test (CTT) that has been used to elicit both written and spoken responses for decades.

Biomarkers.

Background: Lewy body pathology consisting of aggregated alpha-Synuclein (a-Syn) is the hallmark pathology in Parkinson's disease, yet a-Syn aggregates are also commonly observed post-mortem as a co-pathology in Alzheimer's disease (AD) patients. Preclinical research has shown that a-Syn can amplify Ab-associated tau seeding and aggregation, hence a-Syn co-pathology may contribute to the Ab-induced progression of tau pathology in AD. To address this, we combined a novel CSF-based RT-QuIC seed-amplification assay to determine a-Syn positivity, with PET-neuroimaging in a large patient cohort ranging from cognitively normal to dementia, to determine whether a-Syn co-pathology accelerates Ab-driven tau accumulation.

Biomarkers.

Background: Alzheimer's disease (AD) is identified by the accumulation of amyloid β (Aβ) and tau proteins in the brain. The NeuroToolKit offers automated cerebrospinal fluid (CSF) immunoassays of core AD biomarkers and biomarkers of neurodegeneration and synaptic function, including neurofilament light (NfL), SNAP-25, and neuronal pentraxin 2 (NPTX2). This work explores whether these three markers predict pre-dementia cognitive decline synergistically with or after accounting for CSF ptau/Aβ.

Biomarkers.

Background: Alzheimer's disease (AD) is thought to result from a complex cascade of events involving several pathological processes. Recent studies have reported alterations in white matter (WM) microstructure in the early phase of AD, but WM remains understudied. We used a multivariate approach to capture the complexity and heterogeneity of WM pathologies and its links to cognition and AD risk factors in a more holistic manner.

Biomarkers.

Background: The Centiloid framework was developed to harmonize amyloid-PET quantification across radiotracers and processing pipelines to facilitate data sharing and merging; it is now widely used across research and clinical trials. As we just completed the quantification of 10,361 amyloid-PET scans from the largest "real-world" study of amyloid-PET (IDEAS) and are about to release the data, we aimed to compare the distribution of IDEAS Centiloid values with other available datasets.

Method: In IDEAS, amyloid scans were acquired across 343 facilities and centrally processed at UCSF using a PET-only pipeline.

Biomarkers.

Background: To understand the progression of Alzheimer's disease (AD), neuroimaging and biomarker research relies increasingly on sophisticated data analysis techniques that are often restricted to expert lab environments. Here, we demonstrate how complex analyses on modeling tau spreading across interconnected brain regions from our previous studies (e.g.

Biomarkers.

Background: In-vivo detection of neuropathology is critical for early diagnosis of neurodegenerative diseases. Post-mortem brain magnetic resonance imaging (MRI) of pathological protein inclusions could further our ability to detect them in vivo and correlate MRI parameters to histopathological substrates. In this post-mortem study, we aimed to identify MRI correlates of neurodegenerative disease pathology in a brain with various forms of proteinopathies.

Biomarkers.

Background: Florzolotau (APN-1607) tau-PET has shown distinct patterns of binding in patients with AD and 4-repeat tauopathies. We aimed to establish disease-specific tau covariance patterns in AD and PSP/CBS and validate them as user-independent quantitative biomarkers for reference-region-free evaluation of tau-PET in an independent clinical cohort.

Method: We analyzed Florzolotau PET data from four different cohorts.

Public Health.

Background: High-income countries (HICs) are over-represented in current global dementia incidence rates, skewing estimates. Variance in diagnostic methods between HICs and low- and middle-income countries (LMICs) is speculated to contribute to the regional differences in rates. Cohort Studies of Memory in an International Consortium (COSMIC) offers a unique opportunity to address these research inequalities by harmonising data from international studies, including representation from LMICs.

Public Health.

Background: Metabolic syndrome (MetS) has been previously associated with an increased risk of developing dementia. Exploring links between MetS, neuroimaging and cognitive function measures can offer insights into whether MetS adversely affects brain health prior to dementia onset. We sought to examine the association of MetS with brain structure and cognition.

Public Health.

Background: Previous research has shown that the experience of social deprivation is associated with impaired cognition in older adulthood. It has been proposed that this may be explained by social deprivation being associated with a less 'brain-healthy' lifestyle. We thus investigate mediating effects of lifestyle in the association between social deprivation and cognition.

Public Health.

Background: Recent research on preventing cognitive decline has focused on lifestyle interventions, with first studies indicating cognitive benefits and suggesting a positive link between adherence to the interventions and their effectiveness. The purpose of this study was to analyse possible predictors of this very adherence to single components of a multi-domain lifestyle intervention.

Methods: A total of n = 317 participants of the intervention group were included, characterized with an age ≥60 (mean age 68.

Vesicle-Encapsulated Chemosensing Ensembles Allow Monitoring of Transmembrane Uptake Coupled with Enzymatic Reactions.

Compartmentalized models with coupled catalytic networks are considered as "protocells" in the context of research related to the origin of life. To model the kinetics of a simple cellular uptake-metabolism process, we use a compartmentalized protocell system that combines liposome-encapsulated intravesicular reporter pairs with co-encapsulated enzymes to monitor the membrane transport of a substrate (analyte uptake) and its subsequent enzymatic reaction inside the vesicles (metabolism to the product). The intravesicular chemosensing ensembles consist of the macrocycles cucurbit[7]uril or p-sulfonatocalix[4]arene and matching fluorescent dyes to set up suitable reporter pairs.

Public Health.

Background: Dementia risk scores have been suggested a promising surrogate outcome for lifestyle interventions targeting cognitive function and dementia risk. First evidence suggests beneficial effects of multidomain lifestyle interventions on dementia risk scores. We investigated effects of the multidomain AgeWell.

Public Health.

Background: The hypothalamus is the body's principal homeostatic center and plays a crucial role in the modulation of cognition. However, detailed assessments of age and sex effects on hypothalamic substructural integrity and its cognitive correlates across lifespan are still lacking. Therefore, we aimed to investigate the hypothalamic structural integrity in relation to age, sex and cognitive performance across lifespan in the general population.